Jason J. Hamann

Mechanical compression elicits vasodilatation in rat skeletal muscle feed arteries

To date, no satisfactory explanation has been provided for the immediate increase in blood flow to skeletal muscles at the onset of exercise. We hypothesized that rapid vasodilatation is a consequence of release of a vasoactive substance from the endothelium owing to mechanical deformation of the vasculature during contraction. Rat soleus feed arteries were isolated, removed and mounted on micropipettes in a sealed chamber. Arteries were pressurized to 68 mmHg, and luminal diameter was measured using an inverted microscope. Pressure pulses of 600 mmHg were delivered for 1 s, 5 s, and as a series of five repeated 1 s pulses with 1 s between pulses. During application of external pressure the lumen of the artery was completely closed, but immediately following release of pressure the diameter was significantly increased. In intact arteries (series 1, n= 6) for the 1 s pulse, 5 s pulse and series of five 1 s pulses, the peak increases in diameter were, respectively, (mean ±s.e.m.) 16 ± 2, 14 ± 2 and 27 ± 3%, with respective times from release of pressure to peak diameter of 4.1 ± 0.3, 4.6 ± 0.7 and 2.8 ± 0.4 s. In series 2 (n= 9) the arteries increased diameter by 15 ± 2, 15 ± 2 and 30 ± 3% before and by 8 ± 1, 8 ± 1 and 21 ± 2% after removal of the endothelium with air. The important new finding in these experiments is that mechanical compression caused dilatation of skeletal muscle feed arteries with a time course similar to the change in blood flow after a brief muscle contraction. The magnitude of dilatation was not affected by increasing the duration of compression but was enhanced by increasing the number of compressions. Since removal of the endothelium reduced but did not abolish the dilatation in response to mechanical compression, it appears that the dilatation is mediated by both endothelium‐dependent and ‐independent signalling pathways.

Vasodilatation is obligatory for contraction-induced hyperaemia in canine skeletal muscle

There is a rapid increase in blood flow to active skeletal muscle with the onset of exercise, but the mechanism(s) eliciting this increase remains elusive. We hypothesized that the rapid increase in blood flow to active skeletal muscle with the onset of exercise is attributable to vasodilatation as a consequence of smooth muscle hyperpolarization. To test this hypothesis we examined the blood flow response to a brief tetanic contraction in which potassium (K+) was infused intra‐arterially to elevate the [K+]o and clamp the smooth muscle membrane potential within the skeletal muscle vascular bed. In six anaesthetized beagle dogs control contractions increased hindlimb blood flow by 97 ± 14 ml min−1. During K+ infusion the hyperaemic response to contraction was 8 ± 3 ml min−1. Since the hindlimb blood flow was reduced during K+ infusion, a similar reduction in baseline blood flow was produced with phenylephrine infusion. During phenylephrine infusion the hyperaemic response to contraction was preserved (89 ± 23 ml min−1). Recovery contractions performed after the discontinuation of the K+ infusion elicited blood flow responses similar to control (100 ± 11 ml min−1). In a separate experimental protocol using the isolated gastrocnemius muscle of mongrel dogs (n= 6) K+ infusion did not alter force production by the skeletal muscle. Our data indicate that in the absence of vasodilatation, there is virtually no change in blood flow. One implication of this finding is that the muscle pump cannot be responsible for the initial contraction‐induced hyperaemia. We conclude that the increase in blood flow immediately following a single muscle contraction is due to vasodilatation, presumably as a consequence of smooth muscle hyperpolarization.

Frequency and pattern dependence of adrenergic and purinergic vasoconstriction in rat skeletal muscle arteries

Sympathetic nerves fire in bursts followed by brief periods of quiescence. Periods of quiescence may be a valuable part of coding for different neurotransmitters. We compared adrenergic‐ and non‐adrenergic‐mediated vasoconstriction with repeating burst patterns versus constant frequency stimulation. Seventeen rats were killed, and the femoral arteries dissected out and mounted in organ tissue baths at 37°C and pH 7.4. Field stimulation was applied to artery rings from five rats at constant frequencies of 2–6 Hz for 144 impulses. In 12 rats, artery rings were stimulated with two burst pattern protocols consisting of repeating pairs, triplets, quadruplets or sextuplets performed using either 8 or 30 Hz as the instantaneous frequency for a total of 144 impulses. All protocols were repeated with the P2 purinergic antagonist pyridoxal‐phosphate‐6‐azophenyl‐2′4′‐disulphonic acid (PPADs; 0.42 m) or the α1‐antagonist prazosin (1.59 μm). Tension was decreased by the addition of the P2 antagonist PPADs (P < 0.05). Prazosin abolished tension at all constant frequencies (P < 0.05). P2 and α1‐antagonism decreased tension with 8 and 30 Hz burst pattern field stimulation. However, the magnitude of decrease in tension with prazosin was less with burst patterns compared to the same average constant frequencies (P < 0.05). It appears that P2X receptors and α1‐receptors in the femoral artery are sensitive to frequency and patterns of electrical stimulation.

Laser revascularization of ischemic skeletal muscle

BACKGROUNDnClinical trials have shown that transmyocardial laser revascularization is an effective secondary treatment for ischemic heart disease patients. Laser revascularization may also provide an alternative method for treating peripheral vascular disease.nnnMETHODSnThe purpose of this study was to investigate the potential for laser revascularization in ischemic skeletal muscle. Eighteen rabbits (3-4 kg) were instrumented chronically with transit time ultrasound flowprobes on both common iliac arteries. All rabbits performed graded exercise tests on a treadmill where maximal blood flow was recorded. Unilateral hindlimb ischemia was produced by ligation of one femoral artery. At week 3 postligation, 10 rabbits received laser therapy and 8 underwent a sham surgery. In each of four muscles (gracilius, medialis, sartorius, and biceps femoris) 5 to 22 laser channels were created (average = 52 channels per leg).nnnRESULTSnAt week 3 postligation the maximal blood flow of the ischemic limb for the treated group was 64 +/- 3 ml/min (mean +/- SEM) and at 6 weeks postlaser therapy maximal blood flow increased to 75 +/- 5 ml/min. The sham surgery group had a maximal blood flow of 58 +/- 4 ml/min at week 3 postligation and 66 +/- 3 ml/min at week 6 postsham surgery.nnnCONCLUSIONnThese results indicate that laser therapy does not induce angiogenesis and vascular remodeling in the ischemic hindlimb of a rabbit which exceeds that seen with a sham surgery.

Role of Nitric Oxide in Exercise Sympatholysis

The production of nitric oxide is the putative mechanism for the attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during exercise. We hypothesized that nitric oxide synthase blockade would eliminate the reduction in alpha-adrenergic-receptor responsiveness in exercising skeletal muscle. Ten mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective alpha(1)-adrenergic agonist (phenylephrine) or the selective alpha(2)-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Before nitric oxide synthase inhibition with N(G)-nitro-l-arginine methyl ester (l-NAME), intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of -91 +/- 3, -80 +/- 5, and -75 +/- 6% (means +/- SE) at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by -65 +/- 6, -39 +/- 4, and -30 +/- 3%. After l-NAME, intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of -85 +/- 5, -85 +/- 5, and -84 +/- 5%, whereas clonidine reduced vascular conductance by -67 +/- 5, -45 +/- 3, and -35 +/- 3%, at rest, 3 miles/h, and 6 miles/h and 10% grade. alpha(1)-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, alpha(2)-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. Whereas the inhibition of nitric oxide production eliminated the exercise-induced attenuation of alpha(1)-adrenergic-receptor responsiveness, the attenuation of alpha(2)-adrenergic-receptor responsiveness was unaffected. These results suggest that the mechanism of exercise sympatholysis is not entirely mediated by the production of nitric oxide.